The high turnover of mammalian blood cells requires a supply of hematopoietic stem cells that are able to give rise to other blood cell lineages. The immediate progeny of the hematopoietic stem cell are called progenitor cells, and are capable of giving rise to various cell types within one or more lineages, i.e. the erythroid, myeloid and lymphoid lineages. The stem cell and progenitor cell populations constitute only a small percentage of the total number of cells in bone marrow, fetal liver, etc. These populations are of immense interest because of their ability to repopulate the hematopoietic system.
A number of methods have been described in the literature for the purification or enrichment of hematopoietic stem cell and progenitor cell populations. There is significant commercial interest in these methods because hematopoietic progenitors have a number of clinical uses. Progenitor cell transplantation is currently used in conjunction with chemotherapy and radiation for the treatment of leukemia, breast cancer and other tumors. Frequently, autologous transplants are used to avoid the danger of graft rejection, but there is an increased risk of disease reappearance, due to the presence of tumor cells in the engrafting cell population. Transplantation of a more purified source of progenitor cells is therefore preferable.
There is also interest in the use of hematopoietic progenitor cells as a vehicle for gene therapy. Although not yet proven in the clinic, the longevity of hematopoietic stem cells and the dissemination of their progeny in the vasculature are desirable characteristics. A number of vectors, including several retrovirus and adenovirus based constructs, that can transfect hematopoietic stem cells have been described.
Proteins and other cell surface markers found on hematopoietic stem cell and progenitor cell populations are of great interest, as they are useful in preparing reagents for identification, separation and isolation of these populations and in the further characterization of these important cells. Although some antigens are now known that can be used in the identification and separation (positive and negative) of stem cells, such as (for example) the CD 34 antigen, which is found on stem cells but not on mature blood cells, there is a continued need for development of other antigens, particularly one that can simplify the identification and separation of desirable classes and subclasses of cells, especially hematopoietic stem cells and progenitor cells.